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Janus kinase inhibitor Tofacitinib alleviated acute hepatitis induced by lipopolysaccharide/D-galactosamine in mice

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Abstract

Background:

The Janus kinase (JAK) is a crucial intracellular signaling hub for numerous cytokines, which is extensively involved in the activation of inflammatory cascade and the induction of inflammatory injury. JAK inhibition provides protective effects in several inflammation-based disorders, but the potential effects of JAK inhibitor in inflammation-based acute hepatitis remain to be investigated.

Methods and results:

Acute hepatitis is induced by Lipopolysaccharide/D-galactosamine (LPS/D-Gal) in mice with or without the JAK inhibitor Tofacitinib administration. The degree of liver injury, the production of pro-inflammatory cytokines and induction of hepatocytes apoptosis were determined. The results indicated that treatment with Tofacitinib decreased the levels of aminotransferases, attenuated the histological abnormalities in liver and decreased the plasma levels of TNF-α and IL-6 in LPS/D-Gal-insulted mice. In addition, Tofacitinib suppressed the activation of the caspase cascade, decreased the level of cleaved caspase-3, and reduced the count of TUNEL-positive cells.

Conclusion:

Treatment with Tofacitinib alleviated LPS/D-Gal-induced acute hepatitis. JAK maybe become a promising target for the control of inflammation-based liver disorders.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (No.81871606) and the Science and Technology Research Program of Chongqing Municipal Education Commission (No. KJQN201900435).

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Author notes

  1. Xinyue Zhang and Ling Lin contributed equally to this work.

Authors and Affiliations

  1. Department of Pathophysiology, Basic Medical College, Chongqing Medical University, Chongqing, PR China

    Xinyue Zhang, Ling Lin, Longjiang Li, Li Zhang, Li Tang & Yongqiang Yang

  2. Department of Histology and Embryology, Basic Medical College, Chongqing Medical University, Chongqing, PR China

    Kai Hu

  3. Clinical Medical School, Chongqing Medical and Pharmaceutical College, Chongqing, PR China

    Ruyue Shao

  4. Chongqing Engineering Research Center of Pharmaceutical Sciences, Chongqing, PR China

    Ruyue Shao

  5. Department of Pathology, Karamay Central Hosptial of XinJiang Karamay, Karamay, Xinjiang, PR China

    Min Zhu & Yuhua Ma

  6. Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, PR China

    Min Zhu & Yuhua Ma

Authors
  1. Xinyue Zhang
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  2. Ling Lin
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  3. Longjiang Li
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  4. Kai Hu
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  6. Li Zhang
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  7. Li Tang
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  8. Min Zhu
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Contributions

Xinyue Zhang, Li Zhang, and Yongqiang Yang conceived and designed the project. Ling Lin, Longjiang Li and Kai Hu acquired the data. Li Tang, Ruyue Shao and Min Zhu analyzed and interpreted the data. Yuhua Ma, Xinyue Zhang and Yongqiang Yang wrote the paper.

Corresponding authors

Correspondence to Yuhua Ma or Yongqiang Yang.

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Conflict of interest

The authors declared no potential conflicts of interest concerning the research, authorship and/or publication of this article.

Ethical approval

All animal experiments in this study were approved by the Ethics Committee of Chongqing Medical University.

Data accessibility

The data supporting this study’s findings are available from the corresponding author (fyyyq1984@cqmu.edu.cn) upon reasonable request.

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Zhang, X., Lin, L., Li, L. et al. Janus kinase inhibitor Tofacitinib alleviated acute hepatitis induced by lipopolysaccharide/D-galactosamine in mice. Mol Biol Rep 50, 1477–1485 (2023). https://doi.org/10.1007/s11033-022-08086-6

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